Statins - Induced Transaminitis

<b>Introduction </b><br /><br /><ul><li><span style="background: white; text-indent: -0.25in;">The most commonly reported hepatic adverse effect is the phenomenon known as <b>transaminitis</b></span><b style="background-color: white; text-indent: -0.25in;">, </b><span style="background-color: white; text-indent: -0.25in;">in which liver enzyme levels are elevated (transient) in the absence of proven hepatotoxicity and commonly occurs in the first 12 weeks of therapy. </span><span style="background-color: white; text-indent: -0.25in;"> </span></li><li><span style="background-color: white; text-indent: -0.25in;">This class effect is usually asymptomatic, reversible, and dose-related.</span></li><li><span style="background: white; text-indent: -0.25in;">There are changing data on the occurrence of these negative hepatic effects, recommendations on their actual risk, monitoring required, and safety of use in those with preexisting hepatic disorders.</span></li></ul><br /><b>Effects of Statins on The Liver</b><br /><ul><li><span style="background: white; text-indent: -0.25in;">Statins exert a potent inhibition of hepatic 3-hydroxyl-3-methylglutaryl coenzyme A reductase, which accounts for the reduction in LDL cholesterol observed with these drugs.</span></li><li><span style="background: white; text-indent: -0.25in;">Although the underlying mechanism remains unclear, hepatotoxicity may result from changes in the lipid components of the hepatocyte membrane, leading to an increase in its permeability with a subsequent “leakage” of liver enzymes.</span></li><li><span style="background: white; text-indent: -0.25in;">This is supported by the observation that elevations in aminotransferase levels.</span></li></ul><div><br /></div><div class="MsoNormal"><b><span style="line-height: 107%;">Incidence of Elevation of Liver Enzymes During Statin Treatment<span style="font-size: 14pt;"><o:p></o:p></span></span></b></div><ul><li><span style="background: white; text-indent: -0.25in;">The incidence of elevated aminotransferase levels with different types of statins generally <b>did not exceed 3%</b> of the studied patients' sample.</span><span style="text-indent: -0.25in;"> </span></li><li><span style="background: white; text-indent: -0.25in;">There seems to be a <b>direct relationship</b> between the <b>statin dose</b> and the <b>incidence of transaminitis.</b></span><span style="text-indent: -0.25in;"><b> </b></span></li><li>The reported average incidence of elevations in serum aminotransferase levels to >3x ULN was < 1% in patients receiving low to moderate doses.</li><li>Similarly, the incidence of transaminitis increases up to 2% to 3% in those receiving high doses of statins.</li><li><span style="background: white; text-indent: -0.25in;">The incidence of <b>transaminase elevations is similar among all statins,</b> despite their different pharmacokinetic characteristics</span></li><li>Most cases of transaminitis exhibit spontaneous improvement without the need for drug discontinuation, probably a result of the development of adaptation or tolerance.</li></ul><div></div><div><b>Management and Monitoring</b></div><div><b><br /></b></div><div><b><br /></b></div><table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody><tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhZ5Jtpp03r9vmhoH3DVjVy1Er2SxORFkorP2jttTeHcjkkKTRVjQAlDN6eMC3r7pBKcqYcX_guz4of4GeB1w4fHIJUirSIq0D5b1keGjim0t-4G6jSR2dnY5wWc3NbqVNaMkTQkJtUuYU/s1600/Statin+Algorithm.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img alt="" border="0" data-original-height="605" data-original-width="454" height="640" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhZ5Jtpp03r9vmhoH3DVjVy1Er2SxORFkorP2jttTeHcjkkKTRVjQAlDN6eMC3r7pBKcqYcX_guz4of4GeB1w4fHIJUirSIq0D5b1keGjim0t-4G6jSR2dnY5wWc3NbqVNaMkTQkJtUuYU/s640/Statin+Algorithm.jpg" title="Algorithm for management of abnormal liver enzymes before and during statin treatment" width="480" /></a></td></tr><tr><td class="tr-caption" style="text-align: center;">Algorithm for Management of Abnormal Liver Enzymes Before and During Statin Treatment</td></tr></tbody></table><br /><br /><b>Statins in Preexisting Liver Dysfunction</b><br /><div><ul><li>US FDA continues to recommend that statins be contraindicated in patients with chronic liver disease; however, several authors have recommended starting <b>low-dose statin</b> treatment (because of the possible greater incidence of liver enzyme elevations with higher doses) and having levels rechecked 2 weeks later.</li><li><span style="background: white; text-indent: -0.25in;">LFT monitoring should be performed every month for the first 3 to 4 months and 4 times a year thereafter.</span></li><li><span style="font-size: 7pt; font-stretch: normal; font-variant-numeric: normal; line-height: normal;">  </span><span style="background: white; text-indent: -0.25in;">If the levels of transaminases increase to > 3X baseline values, discontinuation of the drug should be considered.</span></li><li>Clinical correlation with worsening of underlying disease, as well as exclusion of alcohol abuse and drug interactions, should be done before attempting permanent discontinuation of the drug. </li><li>Once levels return to baseline, rechallenge can be considered. </li></ul><div><br /></div><div><b>Conclusion</b></div><div><ul></ul><ul><li><span style="background: white;">The latest reviewed data indicate or support the recommendation from US FDA that “all currently marketed statins appear to be associated with a very low risk of serious liver injury.”</span></li><li><span style="background: white;">Clinicians should not withhold statin therapy for patients whose transaminase elevations have no clinical relevance or are attributable to known stable chronic conditions. Evaluating other causes for alteration in LFTs should be made before establishing a causal relationship with a statin agent.</span></li><li><span style="background: white;">Statin use need not be avoided in patients with preexisting liver dysfunction if its use is clearly indicated.</span></li><li>However, as reported in literature, potential of statins to cause significant and serious hepatic effects should not be overlooked in daily clinical practice</li></ul></div><div></div><div><b>References </b></div><div><ul></ul><ol><li><span style="font-family: inherit;">Rossana M. Calderon, MD, Luigi X. Cubeddu, MD, Ronald B. Goldberg, MD, and Eugene R. Schiff, MD. Statins in the Treatment of Dyslipidemia in the Presence of Elevated Liver Aminotransferase Levels: A Therapeutic Dilemma. <i>Mayo Clinic Proceedings 2010 Apr; 85(4): 349–356<b>.</b></i></span></li><li><span style="font-family: inherit; font-size: small;">Jimmy Jose. Statins and its hepatic effects: Newer data, implications, and changing recommendations. <i>J Pharm Bioallied Sci. 2016 Jan-Mar; 8(1): 23–28.</i></span></li><li><span style="font-family: inherit; font-size: small;">Edward Onusko MD. Statins and elevated liver tests: What’s the fuss?.<i>J Fam Pract </i><i>2008 July;57(7):449-452.</i></span></li><li><span style="font-family: inherit; font-size: small;">US Food and Drug Administration (FDA) <span class="ref-journal" style="text-indent: -0.25in;">P<i>h</i><span class="ref-journal">RMA/FDA/ASSLD drug induced hepatotoxicity white paper post marketing considerations: November 2000.</span></span></span></li><li><span style="font-family: inherit; font-size: small;"><span style="background: white none repeat scroll 0% 0%; text-indent: -0.25in;">US Department of Health and Human Services. Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER) </span><span class="ref-journal" style="text-indent: -0.25in;">Guidance for industry: drug-induced liver injury: premarketing clinical evaluation</span><span style="text-indent: -0.25in;"> Published July 2009 </span></span></li></ol></div></div>

general interaction pharmacokinetics side effect Statins - Induced Transaminitis

Introduction  The most commonly reported hepatic adverse effect is the phenomenon known as transaminitis , in which liver enzyme levels are ...

Read more »

Interaction : Calcium and Food

<ul style="margin-top: 0cm;" type="disc"><li class="MsoNormal" style="mso-list: l1 level1 lfo1; tab-stops: list 36.0pt;"><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;">Due to its dependence on stomach acid for absorption, calcium carbonate is absorbed most efficiently when taken with food</span></span></li><li class="MsoNormal" style="mso-list: l1 level1 lfo1; tab-stops: list 36.0pt;"><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;">calcium citrate is absorbed equally well when taken with or without food.</span></span></li><li class="MsoNormal" style="mso-list: l1 level1 lfo1; tab-stops: list 36.0pt;"><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;">Calcium citrate is also useful for people with achlorhydria, inflammatory bowel disease, or absorption disorders</span></span></li><li class="MsoNormal" style="mso-list: l1 level1 lfo1; tab-stops: list 36.0pt;"><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;">Other calcium forms in supplements or fortified foods include gluconate, lactate, and phosphate.</span></span></li></ul><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;"> </span></span><br /><div class="MsoNormal"><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;"><b>Absorption</b></span></span></div><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;"> </span></span><br /><ul style="margin-top: 0cm;" type="disc"><li class="MsoNormal" style="mso-list: l2 level1 lfo2; tab-stops: list 36.0pt;"><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;">Not all calcium consumed is actually absorbed in the gut. Humans absorb about 30% of the calcium in foods, but this varies depending upon the type of food consumed</span></span></li><li class="MsoNormal" style="mso-list: l2 level1 lfo2; tab-stops: list 36.0pt;"><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;">Amount consumed: </span></span></li><ul style="margin-top: 0cm;" type="circle"><li class="MsoNormal" style="mso-list: l2 level2 lfo2; tab-stops: list 72.0pt;"><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;">the efficiency of absorption decreases as calcium intake increases</span></span></li></ul><li class="MsoNormal" style="mso-list: l2 level1 lfo2; tab-stops: list 36.0pt;"><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;">Age: </span></span></li><ul style="margin-top: 0cm;" type="circle"><li class="MsoNormal" style="mso-list: l2 level2 lfo2; tab-stops: list 72.0pt;"><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;">Absorption decreases to 15%–20% in adulthood (though it is increased during pregnancy) and continues to decrease as people age; compared with younger adults, recommended calcium intakes are higher for females older than 50 years and for both males and females older than 70 years</span></span></li></ul><li class="MsoNormal" style="mso-list: l2 level1 lfo2; tab-stops: list 36.0pt;"><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;">Other components in food:</span></span></li><ul style="margin-top: 0cm;" type="circle"><li class="MsoNormal" style="mso-list: l2 level2 lfo2; tab-stops: list 72.0pt;"><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;">phytic acid and oxalic acid, found naturally in some plants, bind to calcium and can inhibit its absorption. </span></span></li><li class="MsoNormal" style="mso-list: l2 level2 lfo2; tab-stops: list 72.0pt;"><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;">Foods with high levels of oxalic acid include spinach, collard greens, sweet potatoes, rhubarb, and beans. </span></span></li><li class="MsoNormal" style="mso-list: l2 level2 lfo2; tab-stops: list 72.0pt;"><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;">Among the foods high in phytic acid are fiber-containing whole-grain products and wheat bran, beans, seeds, nuts, and soy isolates</span></span></li><li class="MsoNormal" style="mso-list: l2 level2 lfo2; tab-stops: list 72.0pt;"><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;">The extent to which these compounds affect calcium absorption varies. Research shows, for example, that eating spinach and milk at the same time reduces absorption of the calcium in milk.</span></span></li><li class="MsoNormal" style="mso-list: l2 level2 lfo2; tab-stops: list 72.0pt;"><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;">In contrast, wheat products (with the exception of wheat bran) do not appear to lower calcium absorption</span></span></li><li class="MsoNormal" style="mso-list: l2 level2 lfo2; tab-stops: list 72.0pt;"><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;">For people who eat a variety of foods, these interactions probably have little or no nutritional consequence and, furthermore, are accounted for in the overall calcium DRIs, which factor in differences in absorption of calcium in mixed diets</span></span></li></ul></ul><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;"> </span></span><br /><div class="MsoNormal"><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;"><b>Elimination</b></span></span></div><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;"> </span></span><br /><ul style="margin-top: 0cm;" type="disc"><li class="MsoNormal" style="mso-list: l0 level1 lfo3; tab-stops: list 36.0pt;"><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;">Sodium and protein intakes:</span></span></li><ul style="margin-top: 0cm;" type="circle"><li class="MsoNormal" style="mso-list: l0 level2 lfo3; tab-stops: list 72.0pt;"><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;">high sodium intake increases urinary calcium excretion. </span></span></li><li class="MsoNormal" style="mso-list: l0 level2 lfo3; tab-stops: list 72.0pt;"><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;">High protein intake also increases calcium excretion and was therefore thought to negatively affect calcium status </span></span></li><li class="MsoNormal" style="mso-list: l0 level2 lfo3; tab-stops: list 72.0pt;"><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;">However, more recent research suggests that high protein intake also increases intestinal calcium absorption, effectively offsetting its effect on calcium excretion, so whole body calcium retention remains unchanged</span></span></li></ul><li class="MsoNormal" style="mso-list: l0 level1 lfo3; tab-stops: list 36.0pt;"><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;">Caffeine intake: </span></span></li><ul style="margin-top: 0cm;" type="circle"><li class="MsoNormal" style="mso-list: l0 level2 lfo3; tab-stops: list 72.0pt;"><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;">this stimulant in coffee and tea can modestly increase calcium excretion and reduce absorption. </span></span></li><li class="MsoNormal" style="mso-list: l0 level2 lfo3; tab-stops: list 72.0pt;"><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;">One cup of regular brewed coffee, for example, causes a loss of only 2–3 mg of calcium</span></span></li></ul><li class="MsoNormal" style="mso-list: l0 level1 lfo3; tab-stops: list 36.0pt;"><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;">Alcohol intake: </span></span></li><ul style="margin-top: 0cm;" type="circle"><li class="MsoNormal" style="mso-list: l0 level2 lfo3; tab-stops: list 72.0pt;"><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;">alcohol intake can affect calcium status by reducing its absorption and by inhibiting enzymes in the liver that help convert vitamin D to its active form. </span></span></li><li class="MsoNormal" style="mso-list: l0 level2 lfo3; tab-stops: list 72.0pt;"><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;">However, the amount of alcohol required to affect calcium status and whether moderate alcohol consumption is helpful or harmful to bone is unknown</span></span></li></ul><li class="MsoNormal" style="mso-list: l0 level1 lfo3; tab-stops: list 36.0pt;"><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;">Fruit and vegetable intakes: </span></span></li><ul style="margin-top: 0cm;" type="circle"><li class="MsoNormal" style="mso-list: l0 level2 lfo3; tab-stops: list 72.0pt;"><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;">metabolic acids produced by diets high in protein and cereal grains increase calcium excretion. </span></span></li><li class="MsoNormal" style="mso-list: l0 level2 lfo3; tab-stops: list 72.0pt;"><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;">Fruits and vegetables, when metabolized, shift the acid/base balance of the body towards the alkaline by producing bicarbonate, which reduces calcium excretion. </span></span></li><li class="MsoNormal" style="mso-list: l0 level2 lfo3; tab-stops: list 72.0pt;"><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;">However, it is unclear if consuming more fruits and vegetables affects bone mineral density. These foods, in addition to reducing calcium excretion, could possibly reduce calcium absorption from the gut and therefore have no net effect on calcium balance</span></span></li></ul></ul><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;"> </span></span><br /><div class="MsoNormal"><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;"><b>Reference:</b></span></span></div><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;"> </span></span><br /><div class="MsoNormal"><span style="font-family: "Trebuchet MS",sans-serif;"><span style="font-family: Verdana,sans-serif;">https://ods.od.nih.gov/factsheets/Calcium-HealthProfessional/ </span></span></div>

interaction Interaction : Calcium and Food

Due to its dependence on stomach acid for absorption, calcium carbonate is absorbed most efficiently when taken with food calcium ...

Read more »

Interaction: Warfarin and Liver

<ul><li><span style="font-size: small;"><span style="font-family: Verdana,sans-serif;">Liver is often seen suggested as a source of vitamin K2 and beef liver in particular has been recommended as a good dietary source. </span></span></li><li><span style="font-size: small;"><span style="font-family: Verdana,sans-serif;">From the tables below it seems that while the beef liver tested contains mk-4, it is not a particularly good source </span></span></li><li><span style="font-size: small;"><span style="font-family: Verdana,sans-serif;">However, most studies have not tested for long-chain menaquinones, mk-6 to mk-13, which are produced by the bacterial fermentation in the stomachs of cattle and provide them with a readily absorbable source of vitamin K2. </span></span></li><li><span style="font-size: small;"><span style="font-family: Verdana,sans-serif;">When absorbed from the gut these reach the liver first where they appear to remain. </span></span></li><li><span style="font-size: small;"><span style="font-family: Verdana,sans-serif;">This can be seen as very little long chain menaquinones were detected in any of the other meat or organs of cattle. </span></span></li><li><span style="font-size: small;"><span style="font-family: Verdana,sans-serif;">The only small study that has tested for these found quite high levels of menaquinones 11, 12, and 13 </span></span></li></ul><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiEFr8nfV_TZGK7S2wOS67bLOoqI3986nn8Z4Y3zSxPbTVPFQC_gxhQvPa8LRcunlesIE-mVivV5urVdegIUEoJJFoMqEyFYVnvCPEQLoX_WaeL4BRtxW-_eTO6zJmZPAvtyy4NkSaMnsVo/s1600/Vitamin+K+Liver2.png.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" data-original-height="662" data-original-width="642" height="640" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiEFr8nfV_TZGK7S2wOS67bLOoqI3986nn8Z4Y3zSxPbTVPFQC_gxhQvPa8LRcunlesIE-mVivV5urVdegIUEoJJFoMqEyFYVnvCPEQLoX_WaeL4BRtxW-_eTO6zJmZPAvtyy4NkSaMnsVo/s640/Vitamin+K+Liver2.png.jpg" width="620" /></a></div><span style="font-size: small;"><span style="font-family: Verdana,sans-serif;"><i>as a comparison, a 100g of cabbage/brocoli has 100mcg of vitamin K, while that of spinach contains 200mcg.</i></span></span><br /><br /><b><span style="font-size: small;"><span style="font-family: Verdana,sans-serif;">References:</span></span></b><br /><ol><li><span style="font-size: small;"><span style="font-family: Verdana,sans-serif;"><span class="fn"><span dir="ltr">Vitamin K</span></span><span class="subtitle"></span><span dir="ltr">. Academic Press</span>, <span dir="ltr">3 Mar 2008</span></span></span></li><li><span style="font-size: small;"><span style="font-family: Verdana,sans-serif;"><span dir="ltr"> </span></span></span><span style="font-size: small;"><span style="font-family: Verdana,sans-serif;">https://honey-guide.com/2014/03/10/menaquinones-k2-and-phylloquinone-k1-content-of-animal-products-and-fermented-foods/ </span></span></li><li><span style="font-size: small;"><span style="font-family: Verdana,sans-serif;">http://apjcn.nhri.org.tw/server/info/books-phds/books/foodfacts/html/data/data3e.html </span></span></li></ol>

interaction Interaction: Warfarin and Liver

Liver is often seen suggested as a source of vitamin K2 and beef liver in particular has been recommended as a good dietary source.  From t...

Read more »

Interaction : Riamet and Akurit 4

<div class="MsoNormal"><b><span style="font-family: "trebuchet ms" , sans-serif;">Availability in Hospital Keningau:</span></b></div><div class="MsoNormal"></div><ul><li><span style="font-family: "trebuchet ms" , sans-serif;">Riamet (Artemether 20mg + Lumenfantrine 120mg)</span></li><li><span style="font-family: "trebuchet ms" , sans-serif;">Akurit-4 (Rifampicin 150mg, Isoniazid 75mg, Pyrazinamide 400mg & Ethambutol HCl 275mg)</span></li></ul><br /><div class="MsoNormal"><b><span style="font-family: "trebuchet ms" , sans-serif;">Interaction:</span></b></div><ul><li style="text-align: justify;"><span style="font-family: "trebuchet ms" , sans-serif;">Oral administration of Rifampicin (600mg) daily, a strong CYP3A4 inducer with Riamet Tablets (6 dose regimen over 3 days) in 6 HIV-1 and Tuberculosis co-infected adults without Malaria resulted in significant decreases in Arthemeter (89%) ,DHA (85%) and Lumenfantrine (68%) when compared to exposure values after Riamet alone.</span></li><li style="text-align: justify;"><span style="font-family: "trebuchet ms" , sans-serif;">Concomitant use of strong inducers such as Rifampicin, Carbamazepine, Phenytoin, St John’s Wart is contraindicated with Riamet.</span></li></ul><div class="MsoNormal" style="text-align: justify;"><b><span style="font-family: "trebuchet ms" , sans-serif;">Alternatives:</span></b></div><ul><li style="text-align: justify;"><span style="font-family: "trebuchet ms" , sans-serif;">A study was done on the effect of combined therapy (rifampicin and quinine) in patients with acute uncomplicated P.Falciparum Malaria. Interestingly, they observed that the parasite clearance was faster with the combination.</span></li><li style="text-align: justify;"><span style="font-family: "trebuchet ms" , sans-serif;">This could be because of the rifampicin antimalarial effect rather than a drug interaction as rifampicin can take several days to induce CYP3A4 activity that is responsible for quinine metabolism.</span></li><li style="text-align: justify;"><span style="font-family: "trebuchet ms" , sans-serif;">After the second day of rifampicin treatment, quinine pre-dose plasma concentrations decreased progressively throughout the treatment period, leading to a fall in quinine activity that may have been the reason for a malaria recrudescence rate five times higher in this group.</span></li><li style="text-align: justify;"><span style="font-family: "trebuchet ms" , sans-serif;">In those patients who are already on rifampicin for the treatment of TB, quinine doses must be increased.</span></li></ul><br /><div class="MsoNormal" style="text-align: justify;"></div><div class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0cm; mso-layout-grid-align: none; text-autospace: none;"><span style="font-family: "trebuchet ms" , sans-serif;">*Quninie Sulphate 300mg is available in Hospital Keningau<o:p></o:p></span></div><div class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0cm; mso-layout-grid-align: none; text-autospace: none;"><span style="font-family: "trebuchet ms" , sans-serif;"><br /></span></div><div class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0cm; mso-layout-grid-align: none; text-autospace: none;"><b><span style="font-family: "trebuchet ms" , sans-serif;">References:</span></b></div><div class="MsoNormal"></div><ol><li><span style="font-family: "trebuchet ms" , sans-serif;">Riamet ® Product leaflet</span></li><li><span style="font-family: "trebuchet ms" , sans-serif;">Mims Malaysia</span></li><li><span style="font-family: "trebuchet ms" , sans-serif;">Sousa, M., Pozniak, A., & Boffito, M. (2008). Pharmacokinetics and pharmacodynamics of drug interactions involving rifampicin, rifabutin and antimalarial drugs. <i>Journal of Antimicrobial Chemotherapy, 62(5), 872-878.</i></span></li></ol><div class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0cm; mso-layout-grid-align: none; text-autospace: none;"></div>

Availability interaction Interaction : Riamet and Akurit 4

Availability in Hospital Keningau: Riamet (Artemether 20mg + Lumenfantrine 120mg) Akurit-4 (Rifampicin 150mg, Isoniazid 75mg, Pyrazinamide 4...

Read more »

Interaction: Denosumab and Pamidronate

<!--[if gte mso 9]><xml> <w:WordDocument> <w:View>Normal</w:View> <w:Zoom>0</w:Zoom> <w:TrackMoves/> <w:TrackFormatting/> <w:PunctuationKerning/> <w:ValidateAgainstSchemas/> <w:SaveIfXMLInvalid>false</w:SaveIfXMLInvalid> <w:IgnoreMixedContent>false</w:IgnoreMixedContent> <w:AlwaysShowPlaceholderText>false</w:AlwaysShowPlaceholderText> <w:DoNotPromoteQF/> <w:LidThemeOther>EN-MY</w:LidThemeOther> <w:LidThemeAsian>X-NONE</w:LidThemeAsian> <w:LidThemeComplexScript>X-NONE</w:LidThemeComplexScript> <w:Compatibility> <w:BreakWrappedTables/> <w:SnapToGridInCell/> <w:WrapTextWithPunct/> <w:UseAsianBreakRules/> <w:DontGrowAutofit/> <w:SplitPgBreakAndParaMark/> <w:DontVertAlignCellWithSp/> <w:DontBreakConstrainedForcedTables/> <w:DontVertAlignInTxbx/> <w:Word11KerningPairs/> <w:CachedColBalance/> </w:Compatibility> <w:BrowserLevel>MicrosoftInternetExplorer4</w:BrowserLevel> <m:mathPr> <m:mathFont m:val="Cambria Math"/> <m:brkBin m:val="before"/> <m:brkBinSub m:val="--"/> <m:smallFrac m:val="off"/> <m:dispDef/> <m:lMargin m:val="0"/> <m:rMargin m:val="0"/> <m:defJc m:val="centerGroup"/> <m:wrapIndent m:val="1440"/> <m:intLim m:val="subSup"/> <m:naryLim m:val="undOvr"/> </m:mathPr></w:WordDocument></xml><![endif]--> <div class="MsoNormal" style="mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><span style="font-family: "Verdana","sans-serif";">Availability</span></b></div><ul type="disc"><li class="MsoNormal" style="line-height: normal; mso-list: l3 level1 lfo1; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";">Pamidronate Disodium 30mg Injection</span></li><li class="MsoNormal" style="line-height: normal; mso-list: l3 level1 lfo1; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";">Denosumab 60mg/ml prefilled syringe</span></li></ul><div class="MsoNormal" style="mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><span style="font-family: "Verdana","sans-serif";">Rationale for Combination use</span></b></div><ul type="disc"><li class="MsoNormal" style="line-height: normal; mso-list: l1 level1 lfo2; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";">Currently no available guidelines practices a combination use</span></li><li class="MsoNormal" style="line-height: normal; mso-list: l1 level1 lfo2; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";">Agents are only used one after the other in cases of refractory to either one of the therapy</span></li></ul><div class="MsoNormal" style="mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><span style="font-family: "Verdana","sans-serif";">Interaction</span></b></div><ul type="disc"><li class="MsoNormal" style="line-height: normal; mso-list: l2 level1 lfo3; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";">Category: Moderate</span></li><li class="MsoNormal" style="line-height: normal; mso-list: l2 level1 lfo3; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";">Osteonecrosis of the jaw (ONJ) has been reported with the use of angiogenesis inhibitors including denosumab, bevacizumab, and sunitinib. </span></li><li class="MsoNormal" style="line-height: normal; mso-list: l2 level1 lfo3; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";">Concomitant exposure with other risk factors such as bisphosphonates (potency, route of administration, and cumulative dose), cancer, chemotherapy, corticosteroids, radiotherapy to the head and neck, dental disease, invasive dental procedures, or poor oral hygiene may increase the risk</span></li><li class="MsoNormal" style="line-height: normal; mso-list: l2 level1 lfo3; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";">For denosumab, the majority of reported cases of ONJ in clinical trials occurred within 5 months after the last dose; in clinical trials, the incidence increased with duration of exposure. </span></li><li class="MsoNormal" style="line-height: normal; mso-list: l2 level1 lfo3; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";">ONJ has been rarely reported in clinical trials with the use of denosumab for osteoporosis.</span></li></ul><div class="MsoNormal" style="mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><span style="font-family: "Verdana","sans-serif";">Management</span></b></div><ul type="disc"><li class="MsoNormal" style="line-height: normal; mso-list: l0 level1 lfo4; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";">Caution is advised if bisphosphonates are used simultaneously or sequentially with denosumab or bevacizumab. </span></li><li class="MsoNormal" style="line-height: normal; mso-list: l0 level1 lfo4; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";">Prior to initiating treatment, a thorough dental examination and appropriate preventive dentistry should be considered. If possible, invasive dental procedures should be avoided in patients who have previously received or are receiving intravenous bisphosphonates. </span></li><li class="MsoNormal" style="line-height: normal; mso-list: l0 level1 lfo4; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";">Good oral hygiene practices should be maintained during treatment. </span></li><li class="MsoNormal" style="line-height: normal; mso-list: l0 level1 lfo4; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";">Patients should be advised to seek medical attention if they experience signs and symptoms of osteonecrosis in the jaw, such as: pain in the mouth, teeth, or jaw, swelling or sores inside the mouth, numbness or a feeling of heaviness in the jaw, loosening of a tooth, or exposure of bone in the jaw. </span></li><li class="MsoNormal" style="line-height: normal; mso-list: l0 level1 lfo4; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";">Temporary interruption of treatment should be considered if clinically appropriate, until the condition resolves.</span></li></ul><div class="MsoNormal" style="mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><span style="font-family: "Verdana","sans-serif";">References:</span></b></div><ol start="1" type="1"><li class="MsoNormal" style="line-height: normal; mso-list: l4 level1 lfo5; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";"><a href="http://www.drugs.com/">www.drugs.com</a></span></li><li class="MsoNormal" style="line-height: normal; mso-list: l4 level1 lfo5; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";"><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4976858/">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4976858/</a></span></li></ol>

interaction Interaction: Denosumab and Pamidronate

Availability Pamidronate Disodium 30mg Injection Denosumab 60mg/ml prefilled syringe Rationale for Combination use Currently no a...

Read more »

Drug Interactions : Antihypertensive & NSAIDS

<!--[if gte mso 9]><xml> <w:WordDocument> <w:View>Normal</w:View> <w:Zoom>0</w:Zoom> <w:TrackMoves/> <w:TrackFormatting/> <w:PunctuationKerning/> <w:ValidateAgainstSchemas/> <w:SaveIfXMLInvalid>false</w:SaveIfXMLInvalid> <w:IgnoreMixedContent>false</w:IgnoreMixedContent> <w:AlwaysShowPlaceholderText>false</w:AlwaysShowPlaceholderText> <w:DoNotPromoteQF/> <w:LidThemeOther>EN-MY</w:LidThemeOther> <w:LidThemeAsian>X-NONE</w:LidThemeAsian> <w:LidThemeComplexScript>X-NONE</w:LidThemeComplexScript> <w:Compatibility> <w:BreakWrappedTables/> <w:SnapToGridInCell/> <w:WrapTextWithPunct/> <w:UseAsianBreakRules/> <w:DontGrowAutofit/> <w:SplitPgBreakAndParaMark/> <w:DontVertAlignCellWithSp/> <w:DontBreakConstrainedForcedTables/> <w:DontVertAlignInTxbx/> <w:Word11KerningPairs/> <w:CachedColBalance/> </w:Compatibility> <w:BrowserLevel>MicrosoftInternetExplorer4</w:BrowserLevel> <m:mathPr> <m:mathFont m:val="Cambria Math"/> <m:brkBin m:val="before"/> <m:brkBinSub m:val="--"/> <m:smallFrac m:val="off"/> <m:dispDef/> <m:lMargin m:val="0"/> <m:rMargin m:val="0"/> <m:defJc m:val="centerGroup"/> <m:wrapIndent m:val="1440"/> <m:intLim m:val="subSup"/> <m:naryLim m:val="undOvr"/> </m:mathPr></w:WordDocument></xml><![endif]--> <ul type="disc"><li class="MsoNormal" style="line-height: normal; mso-list: l3 level1 lfo1; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Arial","sans-serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;">Antihypertensive drugs appear to be affected to variable degrees by NSAIDs.</span><span style="font-family: "Times New Roman","serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;"></span></li><li class="MsoNormal" style="line-height: normal; mso-list: l3 level1 lfo1; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Arial","sans-serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;">Diuretics, angiotensin-converting enzyme inhibitors (ACEIs), beta-blockers, and angiotensin II receptor blockers (ARBs) are most susceptible to the hypotensivenullifying effects of NSAIDs.</span><span style="font-family: "Times New Roman","serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;"></span></li><li class="MsoNormal" style="line-height: normal; mso-list: l3 level1 lfo1; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Arial","sans-serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;">Calcium channel blockers and centrally acting antihypertensives seem to be least affected. </span><span style="font-family: "Times New Roman","serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;"></span></li><li class="MsoNormal" style="line-height: normal; mso-list: l3 level1 lfo1; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Arial","sans-serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;">Although the absolute increase in BP resulting from NSAID coadministration is usually limited to <10 mm Hg, it can result in a 50% reduction in the efficacy of an antihypertensive drug and block the beneficial cardiovascular effects of BP reduction</span><span style="font-family: "Times New Roman","serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;"></span></li></ul><div class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><br /></div><div class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><u><span style="background: white; font-family: "Arial","sans-serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;">Posible Mechanism </span></u></b><span style="font-family: "Times New Roman","serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;"></span></div><ul type="disc"><li class="MsoNormal" style="line-height: normal; mso-list: l2 level1 lfo2; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Arial","sans-serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;">NSAIDs inhibit prostaglandin-mediated vasodilation and promote salt and water retention.</span><span style="font-family: "Times New Roman","serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;"></span></li><li class="MsoNormal" style="line-height: normal; mso-list: l2 level1 lfo2; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="background: white; font-family: "Arial","sans-serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;">Both of these mechanisms may contribute to NSAIDs partially reversing the effects of hypotensive drugs, particularly those agents whose mechanism depends on modulating prostaglandins, renin, or sodium and water balance.</span><span style="font-family: "Times New Roman","serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;"></span></li></ul><div class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><u><span style="font-family: "Arial","sans-serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;">Management of Interactions </span></u></b><span style="font-family: "Times New Roman","serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;"></span></div><div class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><br /></div><ul type="disc"><li class="MsoNormal" style="line-height: normal; mso-list: l1 level1 lfo3; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Arial","sans-serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;">Short courses of NSAID therapy (ie, less than a week or 2), even with daily NSAID administration, are unlikely to cause a clinically important increase in a patient's BP</span><span style="font-family: "Times New Roman","serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;"></span></li><li class="MsoNormal" style="line-height: normal; mso-list: l1 level1 lfo3; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Arial","sans-serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;">Short courses of NSAIDs may cause exacerbation of heart failure. Patients should be counseled to report any symptom changes during NSAID administration.</span><span style="font-family: "Times New Roman","serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;"></span></li><li class="MsoNormal" style="line-height: normal; mso-list: l1 level1 lfo3; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Arial","sans-serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;">Low-dose aspirin therapy does not appear to affect the efficacy of antihypertensive drugs or diuretics</span><span style="font-family: "Times New Roman","serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;"></span></li><li class="MsoNormal" style="line-height: normal; mso-list: l1 level1 lfo3; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Arial","sans-serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;">Switching to an antihypertensive drug not as susceptible to the blunting effects of NSAIDs should be considered for patients requiring chronic NSAID therapy.</span><span style="font-family: "Times New Roman","serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;"></span></li><li class="MsoNormal" style="line-height: normal; mso-list: l1 level1 lfo3; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Arial","sans-serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;">Consider alternative analgesics, such as acetaminophen, tramadol, or narcotic analgesics, for patients requiring analgesics who are unable to have their antihypertensive regimen altered</span><span style="font-family: "Times New Roman","serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;"></span></li><li class="MsoNormal" style="line-height: normal; mso-list: l1 level1 lfo3; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Arial","sans-serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;">Monitor BP of patients taking NSAIDs for several weeks to determine if they are candidates for drug regimen adjustments. Also, be alert for signs of fluid retention, such as weight gain or peripheral edema. </span><span style="font-family: "Times New Roman","serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;"></span></li></ul><div class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><span style="font-family: "Arial","sans-serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;">Reference ; </span></b><span style="font-family: "Times New Roman","serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;"></span></div><ol start="1" type="1"><li class="MsoNormal" style="line-height: normal; mso-list: l0 level1 lfo4; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Arial","sans-serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;">http://www.pharmacytimes.com/publications/issue/2006/2006-04/2006-04-5484</span><span style="font-family: "Times New Roman","serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;"></span></li><li class="MsoNormal" style="line-height: normal; mso-list: l0 level1 lfo4; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Arial","sans-serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;">https://www.ncbi.nlm.nih.gov/pubmed/9397294</span><span style="font-family: "Times New Roman","serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;"></span></li><li class="MsoNormal" style="line-height: normal; mso-list: l0 level1 lfo4; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Arial","sans-serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;">http://www.medscape.com/features/slideshow/dangerous-drug-combinations#page=7</span><span style="font-family: "Times New Roman","serif"; font-size: 12.0pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-MY;"></span></li></ol>

interaction Drug Interactions : Antihypertensive & NSAIDS

Antihypertensive drugs appear to be affected to variable degrees by NSAIDs. Diuretics, angiotensin-converting enzyme inhibitors (...

Read more »

Interaction: Benadryl and Antihistamine

<!--[if gte mso 9]><xml> <w:WordDocument> <w:View>Normal</w:View> <w:Zoom>0</w:Zoom> <w:TrackMoves/> <w:TrackFormatting/> <w:PunctuationKerning/> <w:ValidateAgainstSchemas/> <w:SaveIfXMLInvalid>false</w:SaveIfXMLInvalid> <w:IgnoreMixedContent>false</w:IgnoreMixedContent> <w:AlwaysShowPlaceholderText>false</w:AlwaysShowPlaceholderText> <w:DoNotPromoteQF/> <w:LidThemeOther>EN-MY</w:LidThemeOther> <w:LidThemeAsian>X-NONE</w:LidThemeAsian> <w:LidThemeComplexScript>X-NONE</w:LidThemeComplexScript> <w:Compatibility> <w:BreakWrappedTables/> <w:SnapToGridInCell/> <w:WrapTextWithPunct/> <w:UseAsianBreakRules/> <w:DontGrowAutofit/> <w:SplitPgBreakAndParaMark/> <w:DontVertAlignCellWithSp/> <w:DontBreakConstrainedForcedTables/> <w:DontVertAlignInTxbx/> <w:Word11KerningPairs/> <w:CachedColBalance/> </w:Compatibility> <w:BrowserLevel>MicrosoftInternetExplorer4</w:BrowserLevel> <m:mathPr> <m:mathFont m:val="Cambria Math"/> <m:brkBin m:val="before"/> <m:brkBinSub m:val="--"/> <m:smallFrac m:val="off"/> <m:dispDef/> <m:lMargin m:val="0"/> <m:rMargin m:val="0"/> <m:defJc m:val="centerGroup"/> <m:wrapIndent m:val="1440"/> <m:intLim m:val="subSup"/> <m:naryLim m:val="undOvr"/> </m:mathPr></w:WordDocument></xml><![endif]--> <ul type="disc"><li class="MsoNormal" style="line-height: normal; mso-list: l1 level1 lfo1; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";">Benadryl = Diphenhydramine (antihistamine) + Ammnium Chloride (expectorant)</span></li></ul><div class="MsoNormal" style="mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><span style="font-family: "Verdana","sans-serif";">Mechanism of action</span></b></div><ul type="disc"><li class="MsoNormal" style="line-height: normal; mso-list: l3 level1 lfo2; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";">Diphenhydramine provide symptomatic relief in cases of allergic cough by reducing the body’s production of histamine</span></li><li class="MsoNormal" style="line-height: normal; mso-list: l3 level1 lfo2; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";">Ammonium chloride and ammonium carbonate have an irritant effect on mucous membranes and are considered to have expectorant properties</span></li></ul><div class="MsoNormal" style="mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><span style="font-family: "Verdana","sans-serif";">Interactions</span></b></div><ul type="disc"><li class="MsoNormal" style="line-height: normal; mso-list: l4 level1 lfo3; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";">Level of interaction: Moderate </span></li><li class="MsoNormal" style="line-height: normal; mso-list: l4 level1 lfo3; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";">Usually avoid combinations; use it only under special circumstances</span></li><li class="MsoNormal" style="line-height: normal; mso-list: l4 level1 lfo3; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";">Excessive parasympatholytic effects may result in paralytic ileus, hyperthermia, heat stroke, and the anticholinergic intoxication syndrome. </span></li><li class="MsoNormal" style="line-height: normal; mso-list: l4 level1 lfo3; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";">Peripheral symptoms of intoxication commonly include mydriasis, blurred vision, flushed face, fever, dry skin and mucous membranes, tachycardia, urinary retention, and constipation. </span></li><li class="MsoNormal" style="line-height: normal; mso-list: l4 level1 lfo3; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";">Central symptoms may include memory loss, disorientation, incoherence, hallucinations, psychosis, delirium, hyperactivity, twitching or jerking movements, stereotypy, and seizures. </span></li><li class="MsoNormal" style="line-height: normal; mso-list: l4 level1 lfo3; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";">Central nervous system-depressant effects may also be additively or synergistically increased when these agents are combined, especially in elderly or debilitated patients</span></li></ul><div class="MsoNormal" style="mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><span style="font-family: "Verdana","sans-serif";">Second Generation Antihistamine</span></b></div><ul type="disc"><li class="MsoNormal" style="line-height: normal; mso-list: l2 level1 lfo4; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";"> example: Loratidine, Cetirizine </span></li><li class="MsoNormal" style="line-height: normal; mso-list: l2 level1 lfo4; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";">Benadryl and loratidine are both antihistamines and work similarly in the body</span></li><li class="MsoNormal" style="line-height: normal; mso-list: l2 level1 lfo4; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";">loratidine is long-acting drug, so if they are taken together their effects will overlap and patients may duplicate the active drug of each medication</span></li><li class="MsoNormal" style="line-height: normal; mso-list: l2 level1 lfo4; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";">If patients have uncontrolled allergies, combination of Benadryl and loratidine may be a good solution, but only if they are taken in different times of a day. </span></li><li class="MsoNormal" style="line-height: normal; mso-list: l2 level1 lfo4; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";">loratidine should be taken in the morning due to its long-acting and no-sedative properties while Benadryl should be taken at night since it has sedative properties, so it can help patients with uncontrolled allergy symptoms (such as unbearable itches) to fall asleep easier.</span></li><li class="MsoNormal" style="line-height: normal; mso-list: l2 level1 lfo4; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";">The table below shows the incidence of side effects after Benadryl and loratidine administration in recommendable doses. The incidence can be increased if these drugs are overdosed or taken together.</span></li></ul><table border="1" cellpadding="0" class="MsoNormalTable" style="border: solid windowtext 1.0pt; mso-cellspacing: 1.5pt; mso-padding-alt: 0cm 0cm 0cm 0cm; mso-yfti-tbllook: 1184;"> <tbody><tr style="mso-yfti-firstrow: yes; mso-yfti-irow: 0;"> <td style="border: solid windowtext 1.0pt; padding: .75pt .75pt .75pt .75pt; width: 113.9pt;" width="152"> <div class="MsoNormal" style="mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><span style="font-family: "Verdana","sans-serif";">Incidence</span></b><span style="font-size: 12.0pt; line-height: 115%;"></span></div></td> <td style="border: solid windowtext 1.0pt; padding: .75pt .75pt .75pt .75pt; width: 295.45pt;" width="394"> <div class="MsoNormal" style="mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><span style="font-family: "Verdana","sans-serif";">Side effects</span></b><span style="font-size: 12.0pt; line-height: 115%;"></span></div></td> </tr><tr style="mso-yfti-irow: 1;"> <td style="border: solid windowtext 1.0pt; padding: .75pt .75pt .75pt .75pt; width: 113.9pt;" width="152"> <div class="MsoNormal" style="mso-margin-top-alt: auto;"><span style="font-family: "Verdana","sans-serif";">10-15% (very common)</span><span style="font-size: 12.0pt; line-height: 115%;"></span></div></td> <td style="border: solid windowtext 1.0pt; padding: .75pt .75pt .75pt .75pt; width: 295.45pt;" width="394"> <div class="MsoNormal" style="mso-margin-top-alt: auto;"><span style="font-family: "Verdana","sans-serif";">Headache</span><span style="font-size: 12.0pt; line-height: 115%;"></span></div></td> </tr><tr style="mso-yfti-irow: 2;"> <td style="border: solid windowtext 1.0pt; padding: .75pt .75pt .75pt .75pt; width: 113.9pt;" width="152"> <div class="MsoNormal" style="mso-margin-top-alt: auto;"><span style="font-family: "Verdana","sans-serif";">1-10% (common)</span><span style="font-size: 12.0pt; line-height: 115%;"></span></div></td> <td style="border: solid windowtext 1.0pt; padding: .75pt .75pt .75pt .75pt; width: 295.45pt;" width="394"> <div class="MsoNormal" style="mso-margin-top-alt: auto;"><span style="font-family: "Verdana","sans-serif";">Nervousness, Malaise, Somnolence, Drowsiness, Fatigue, Dry mouth, Hyperkinesia, Diarrhea, Dysphonia, Abdominal pain, Conjunctivitis, Dysmenorrhea, Dizziness, Pain in extremity, Somnolence, Rhinorrhea, Pyrexia, Stomach discomfort</span><span style="font-size: 12.0pt; line-height: 115%;"></span></div></td> </tr><tr style="mso-yfti-irow: 3; mso-yfti-lastrow: yes;"> <td style="border: solid windowtext 1.0pt; padding: .75pt .75pt .75pt .75pt; width: 113.9pt;" width="152"> <div class="MsoNormal" style="mso-margin-top-alt: auto;"><span style="font-family: "Verdana","sans-serif";">Frequency Not Defined</span><span style="font-size: 12.0pt; line-height: 115%;"></span></div></td> <td style="border: solid windowtext 1.0pt; padding: .75pt .75pt .75pt .75pt; width: 295.45pt;" width="394"> <div class="MsoNormal" style="mso-margin-top-alt: auto;"><span style="font-family: "Verdana","sans-serif";">Xerostomia, Confusion, Dry nasal mucosa, Pharyngeal dryness, Agranulocytosis, Thrombocytopenia, Convulsions, Hypotension, Palpitations, Urinary retention, Neuritis, Diplopia, Tinnitus, Arthralgia, Myalgia, Hemolytic anemia,</span><span style="font-size: 12.0pt; line-height: 115%;"></span></div></td> </tr></tbody></table><div class="MsoNormal" style="mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><span style="font-family: "Verdana","sans-serif";">Recommendations:</span></b></div><ul type="disc"><li class="MsoNormal" style="line-height: normal; mso-list: l0 level1 lfo5; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";">Usually avoid combinations; use it only under special circumstances</span></li><li class="MsoNormal" style="line-height: normal; mso-list: l0 level1 lfo5; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";">If there is no heart, blood pressure, urinary or kidney contraindications and the use is indicated (severe allergic reactions) this combination will not likely be a problem. </span></li><li class="MsoNormal" style="line-height: normal; mso-list: l0 level1 lfo5; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";">Monitor for signs of overdose / side effects</span></li></ul><div class="MsoNormal" style="mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><span style="font-family: "Verdana","sans-serif";">References:</span></b></div><ol start="1" type="1"><li class="MsoNormal" style="line-height: normal; mso-list: l5 level1 lfo6; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";"><a href="https://www.drugs.com/drug-interactions/benadryl-with-chlor-trimeton">https://www.drugs.com/drug-interactions/benadryl-with-chlor-trimeton</a></span></li><li class="MsoNormal" style="line-height: normal; mso-list: l5 level1 lfo6; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";"><a href="http://www.thehealthsite.com/diseases-conditions/whats-in-a-cough-syrup/">http://www.thehealthsite.com/diseases-conditions/whats-in-a-cough-syrup/</a></span></li><li class="MsoNormal" style="line-height: normal; mso-list: l5 level1 lfo6; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";"><a href="https://www.medicines.org.uk/emc/medicine/11171">https://www.medicines.org.uk/emc/medicine/11171</a></span></li><li class="MsoNormal" style="line-height: normal; mso-list: l5 level1 lfo6; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Verdana","sans-serif";"><a href="http://drugsdetails.com/can-you-take-benadryl-and-claritin-together/">http://drugsdetails.com/can-you-take-benadryl-and-claritin-together/</a></span></li></ol>

interaction other Interaction: Benadryl and Antihistamine

Benadryl = Diphenhydramine (antihistamine) + Ammnium Chloride (expectorant) Mechanism of action Diphenhydramine provide symptomat...

Read more »